PKU is an inherited disease, so newborns are born with hyperphenylalaninemia, but because they are not fed, the blood phenylalanine and its harmful metabolites are not at high concentrations, so there are no clinical signs at birth. If a newborn is not screened for phenylketonuria, the clinical symptoms will gradually appear when the blood phenylalanine and its metabolites are gradually increased with the prolongation of feeding time. The main clinical manifestations are: 1. Growth retardation: In addition to physical growth retardation, the main manifestation is the retardation of intellectual development. The IQ is lower than that of normal infants of the same age, and can appear at 4-9 months after birth. In severe cases, the IQ is below 50, and more than 14% of children reach the level of idiocy, and the language development disorder is especially obvious. These manifestations suggest brain developmental disorders. Restriction of phenylalanine intake in newborns can prevent mental retardation, and children with severe PKU have higher blood phenylalanine concentrations than those with milder forms, so it can be assumed that mental retardation is related to phenylalanine toxicity, but the more detailed pathophysiological mechanisms remain unclear. 2. Neuropsychiatric manifestations: cerebellar malformations due to cerebral atrophy, recurrent convulsions, but decreasing with age. The muscle tone is increased and the reflexes are hyperactive. There is often excitement and restlessness, hyperactivity and abnormal behavior. 3, skin and hair manifestations: skin is often dry, prone to eczema and skin scratching syndrome. Due to the inhibition of tyrosinase, melanin synthesis is reduced, so the affected children’s hair color is light and brown. 4.Other: Due to the lack of phenylalanine hydroxylase, phenylalanine produces phenyl lactic acid and phenylacetic acid from another pathway, which is excreted from sweat and urine and has a musty odor (or rat odor). In general, the clinical manifestations correlate with the type of PAH gene mutation and the severity of the clinical phenotype, with cofactor deficiency having a milder clinical phenotype than PAH protein abnormalities.